Macrolide antibiotics such as troleandomycin (TAO) have been used in the treatment of severe asthma. Clarithromycin (Clar), a new macrolide antibiotic, is being used with increasing frequency in patients with poorly controlled asthma. We thus sought to determine whether Clar displays anti-inflammatory effects by measuring its ability to suppress PHA-induced lymphocyte proliferation (LP). Peripheral blood mononuclear cells from 5 asthmatics were co-incubated with PHA (5 mg/ml) & Clar (1, 10, and 20 mg/ml) in the presence and absence of increasing concentrations of Dexamethasone (Dex). Clar (20 mg/ml) alone resulted in suppression of proliferation, & an additive effect was noted when Clar was co-incubated with Dex (table; p = ANOVA 0 vs 20). Since macrolides can alter glucocorticoid metabolism, we also determined the effect of Clar on methylprednisolone (MPn) & prednisolone (Pn) clearance (CL). 12 hr pharmacokinetic studies (MPn, Pn 40 mg/1.73 m2) were performed prior to & after a 7 d course of Clar. Clar therapy resulted in a 65% reduction in MPn CL (375.8+/-36 vs 130.0+/-5 ml/min/1.73 m2; p=0.003) while having no effect on Pn CL (238.5+/-17 vs. 245.0+/-14 ml/min/1.73 m2). We conclude that Clar causes significant inhibition of LP alone and amplifies the inhibition with Dex. In addition, Clar therapy results in a significant reduction in MPn CL but not Pn CL. This delay in MPn CL, along with the effect on LP may contribute to the beneficial effects of Clar in steroid dependent asthma. In addition, long-term Clar therapy in patients on chronic MPn therapy may increase their risk for steroid-induced adverse effects. There were no serious adverse effects in any subject. We have not published anything with regard to this protocol as it is currently in progress.